the reversible quiescent state that some young cells undergo in the absence of growth factors. The role of replicative senescence in aging of the organism remains controversial, but correlative evidence suggests that it is an in vitro manifestation of an in vivo phenomenon. First, the replicative capacity of cells cultured from old donors is less than that of young donors, suggesting that cells keep track of the number of cell doublings that they have undergone in vivo. Second, the replicative capacity of cells is roughly proportional to the maximum life span of the animals from which they originated. A third line of evidence comes from the study of diseases, such as Werner syndrome (WS), that mimic premature aging. Fibroblasts obtained from WS patients senesce much earlier than normal age-matched controls (Norwood et al. 1979). The WS gene (WRN) has recently been cloned and displays homology to some DNA helicases, although all mutations thus far identified map outside the helicase region, suggesting other possible functions for this protein (Yu et al. 1996). Two predominant models have been suggested to explain the loss of proliferation in senescence. The first proposes that cellular aging results from the accumulation of errors that occur, perhaps, as a result of either impaired DNA repair mechanisms or inadequate free radical‐scavenging abilities. Thus, the cell is seen as passive in the aging process, although it may be able to regulate the process by repairing or removing damaged cellular components. The second model proposes that cells age according to an intrinsic genetic program and, hence, suggests that cells are active participants in their own aging. The majority of the data described below implicate genetic factors in the activation of cellular senescence.